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March 17, 2014 -- PET imaging with sodium fluoride (NaF) changed treatment in more than half of men with prostate cancer and could prove to be a better tool than bone scintigraphy, according to an analysis from the National Oncologic PET Registry (NOPR) published online February 27 in the Journal of Nuclear Medicine.

Use of NaF-PET shifted management plans to treatment for 77% of initial staging patients, 52% of men with suspected first osseous metastases, and 71% of those with suspected progression of osseous metastases. There were definite findings of bone metastasis in 14%, 29%, and 76% of the patients in the three groups, respectively.

"After NaF-PET, referring physicians also reported that 70% to 80% of patients would avoid additional noninvasive imaging and that plans to gather additional information (biopsy or more imaging) would be necessary in only 7% to 12%," lead author Dr. Bruce Hillner and colleagues wrote. "These data reflect referring physicians' confidence (or overconfidence) in NaF-PET's value in stratifying risk and their willingness to make definitive plans immediately" (JNM, February 27, 2014).

Hillner is from the department of internal medicine and the Massey Cancer Center at Virginia Commonwealth University, and he is also a former NOPR co-chairman.

NOPR legacy

The 8-year-old initiative known as NOPR began to wind down its operation after the U.S. Centers for Medicare and Medicaid Services (CMS) announced in June 2013 that it would halt the data collection requirement for all FDG-PET oncologic indications as a condition of reimbursement.

However, NOPR has continued to collect information on NaF-PET since February 2011 to gather evidence on its efficacy in patients with suspected or known osseous metastasis in any cancer type. Conventional bone scintigraphy traditionally has been the first choice in these applications, but it offers limited sensitivity, especially for low-volume metastases, and limited specificity due to degenerative changes. NaF-PET, with or without CT, has become an increasingly popular alternative.

Much like NOPR did with FDG-PET, the registry's NaF-PET data collection included a questionnaire to ascertain physicians' intended oncologic treatment and the NaF-PET results. In NOPR's NaF-PET registry, 72% of patients have pathologically confirmed prostate cancer.

The initial period of NaF-PET data collection was a "learning phase for interpreting physicians unfamiliar" with the modality, the authors wrote. Still, NOPR garnered 7,154 scans from 633 facilities in 2011. In 2012, total scans from participating facilities increased to 7,794. In both years, approximately 50 facilities accounted for 50% of the patients, and approximately 180 facilities performed 10 NaF-PET scans or more per year.

In the cohort used for the current study, 1,024 NaF-PET scans were performed for initial staging, 1,997 for suspected first osseous metastasis, and 510 for suspected progression of osseous metastasis.

The median age of the subjects in the three categories ranged from 73 to 76 years, two to three years older than NOPR's FDG-PET cohort. No symptoms or other abnormalities were noted before NaF-PET in 62% of men referred for initial staging, compared with 13% to 15% of those referred for suspected first osseous metastasis or suspected progression of osseous metastasis.

An elevated or rising prostate-specific antigen (PSA) level was the sole indication in 47% of men with suspected first osseous metastasis and in 37% of those with suspected progression of osseous metastasis. Bone pain alone was noted in 17% of suspected first osseous metastasis cases and in 24% of men with suspected progression of osseous metastasis.

Hillner and colleagues wrote that they were not surprised that for 31% of men undergoing initial staging with NaF-PET, referring physicians were unwilling to estimate the stage of prostate cancer, as bone scintigraphy was needed to complete the evaluation.

"However, we did not anticipate that 38% of men imaged for suspected first osseous metastasis would have their stage listed as unknown," they wrote. "We also suspect that many of the 7% of men imaged for suspected progression of osseous metastasis, with stage listed as no evidence of disease or as only local/regional disease, were misclassified instances of imaging for suspected first osseous metastasis."

Before and after NaF-PET

Before NaF-PET, physicians estimated that metastatic disease was present in approximately 8% of the initial staging group, 34% of the suspected first osseous metastasis group, and 81% of those with suspected progression of osseous metastasis.

If NaF-PET were unavailable, physicians would have used bone scintigraphy to assess 87% to 92% of patients among the three groups.

Approximately one-third of men scanned for suspected first osseous metastasis or suspected progression of osseous metastasis had previously received bone scintigraphy. However, approximately 70% of those exams occurred more than one year prior to NaF-PET.

"When the interval between bone scintigraphy and NaF-PET was less than 90 days, 35% (26/75) of NaF-PET scans showed more evidence of bone metastasis than did bone scintigraphy," the authors wrote.

When the time difference between NaF-PET and bone scintigraphy was less than 180 days, 40% (67/167) of men with suspected first osseous metastasis and 76% (56/73) of those with suspected progression of osseous metastasis showed more extensive disease.

Overall, 50% to 57% of patients for each indication had a pre-PET cancer management plan of a different imaging exam. Body CT was most common at 21% to 24%, body MRI ranged from 9% to 17%, and FDG-PET ranged from 12% to 16% of men across the three groups.